Aaptamine derivatives with CDK2 inhibitory activities from the South China Sea sponge Aaptos suberitoides.
Nat Prod Res
; 36(24): 6215-6223, 2022 Dec.
Article
em En
| MEDLINE
| ID: mdl-35007168
ABSTRACT
Three new aaptamines (1-3) together with two known derivatives (4-5) were isolated from the South China Sea sponge Aaptos suberitoides. The structures of all compounds were unambiguously elucidated by spectroscopic analyses as well as the comparison with literature data. All the compounds were evaluated for their cytotoxic activities against five human cancer cell lines including H1299, H520, SCG7901, CNE-2 and SW680 cells. As a result, compounds 3-5 showed moderate cytotoxicities against H1299 and H520 cells with IC50 values ranging from 12.9 to 20.6 µg/mL. Besides, compounds 3-5 also showed potent inhibitory activities toward cyclin-dependent kinase-2 (CDK2) with IC50 values of 14.3, 3.0 and 6.0 µg/mL, respectively. In addition, compounds 3-5 significantly induced G1 arrests of H1299 cells at low concentrations. Drug affinity responsive target stability (DARTS) experiments were carried out and further demonstrated that compound 3 could effectively bind with CDK2 protein and protect it from the degradation by pronase.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Naftiridinas
/
Antineoplásicos
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
Nat Prod Res
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China